All soft tissue wounds, regardless of size, heal in a similar manner. The central avascular wound space is hypoxic, acidotic, hypercarbic, hypoglycemic, hyperkalemic and has high lactate levels. The central hypoxic dead space is populated exclusively with monocytes which become wound macrophages. Previous work has shown that the presence of the hypoxic central dead space is mandatory for the wound healing process to continue and in vitro experimentation using macrophages showed that hypoxia (15 mm Hg p02) stimulated macrophages to produce angiogenesis factor activity. Raising the p02 to 40 mm Hg decreased the amount of angiogenesis activity and raising it further above 40 mm Hg totally inhibited the secretion of angiogenesis factor from the macrophages. Our present research objectives are to further define the environmental conditions which control macrophage angiogenesis, growth factor production and plasminogen activator production. We will alter the pH, p02, pCO2, glucose, potassium and lactate levels in cultured rabbit bone marrow macrophages. Conditioned media will be assayed for plasminogen activator activity, angiogenesis factor and mitogenic activity for fibroblasts and capillary endothelial cells. The results of these experiments will allow us to more fully understand the effect of local environments on the macrophage production of factors which regulate angiogenesis and local connective tissue responses in tumor growth, atherogenesis, adaptation to exercise and changing pO2's due to elevation and the regulation of fibroblasts after inflammation.